Lentiviral Vector Development for ADA-SCID
Adenosine deaminase (ADA) deficiency is caused by a purine metabolic dysfunction, resulting in severe combined immunodeficiency (SCID) and multiple organ damage. Lentiviral vector (LV)-based gene therapy (GT) has recently been used with success in correcting the immune defects. With Ph.D. level scientists in LV development, Creative Biolabs is dedicated to serving every unique need of LV development for ADA-SCID.
The Background of ADA-SCID
ADA-SCID is a severe primary immunodeficiency characterized by impaired T-cell, B-cell, and NK-cell development, and accounts for 15-20% of all cases of SCID. The lack of ADA causes an accumulation of purine metabolites in the plasma, lymphoid tissues, and red blood cells. Suffering from lymphopenia, absent cellular and humoral immunity, patients with ADA-SCID failure to thrive, and suffer recurrent infections. Moreover, hepatic, renal, lung, skeletal and neurologic abnormalities have been observed in some patients, which indicates that the disease should be considered as a systemic metabolic disorder.
Treatment of ADA-SCID
Like other forms of SCID, bone marrow transplantation from a human leukocyte antigen-identical sibling donor is an effective treatment, but transplants from alternative donors are associated with high morbidity and mortality. Enzyme replacement therapy with bovine ADA conjugated to polyethylene glycol provides adequate metabolic detoxification but often with insufficient immune reconstitution, with the risk of developing neutralizing antibodies and autoimmunity.
Recently, the therapeutic efficacy of gene therapy has been investigated in the absence of enzyme replacement therapy. Results of this trial showed that GT with bone marrow CD34+ cells resulted in the correction of both the immune and metabolic defects of ADA-SCID children pretreated with low-intensity conditioning. However, the adverse events occur in one of the SCID-X1 GT trials have raised general concerns on the potential risks of gammaretroviral vectors. Self-inactivating (SIN) LVs based on human immunodeficiency virus (HIV) have an advanced safety profile over non-SIN gammaretroviral vectors and may thus reduce the risk of insertional oncogenesis. Moreover, LVs have been shown to be safer than gammaretroviral vectors in transferring human candidate hematopoietic stem cells and maintaining sustained transgenes expression.
LV Development for ADA-SCID at Creative Biolabs
Creative Biolabs hopes to construct better gene therapy delivery vectors that may correct both the immune system and non-immune system problems. Our scientists have developed an improved LV system carrying a functional ADA gene to correct the genetic defect. This gene encodes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. By collecting an individual's stem cells and modifying them with an LV, the gene-corrected cells can be returned to the patients to help produce normal healthy immune cells.
Key Advantages of Our Service:
- LV system with improved safety profiles
- LV system carrying a functional ADA gene driven by a special promoter
- Powered by a proven, first-in-class technology
- Best after-sale service
The highly experienced scientists and quality professionals at Creative Biolabs are here to assist you with LV development for ADA-SCID. We offer turn-key or ala carte services customized to our client's needs. Please contact us for more information and a detailed quote.
